Procedures and outcomes in epilepsy surgery Flashcards
Reasons for epilepsy surgery aka risks of ongoing seizures
Although surgery has risks, there are several reasons to consider it for patients with epilepsy. First is the possibility of harm to the patient if surgery is not done, because of continued sei- zures. In a study in 1997, Buck and coworkers [1] found that of 300 patients with at least one seizure in the previous year, 24% had sustained a head injury, 16% had burned or scalded them- selves, 14% had a seizure while bathing or swimming with the risk of drowning, 10% had a dental injury, and 6% had a fracture.
Second, beyond actual injury is the important entity SUDEP (sudden unexpected death in epi- lepsy patients), an entity that may be more common in patients with more generalized con- vulsive seizures and in patients in their third through fifth decades of life. The reason for death in these patients is not known, but it is clear that patients with seizures, particularly with intract- able seizures, can be found dead without a clear explanation other than the fact that they have epilepsy.
Third are the effects that ongoing seizures, particularly those affecting consciousness, have on a person’s daily life. One cannot drive. One may have a seizure in public or in an unfamiliar situation and be unable to care for oneself. Those nearby might react in way that could add addi- tional harm or danger.
Fourth are risks related to side effects of anticonvulsants, particularly if patients have fre- quent seizures with the need for higher doses or for additional numbers of medications. Addi- tionally, for women of childbearing age, anti- convulsants impose risks on a developing fetus, and, for young children, seizures and medica- tions impose risks on development.
Over the last several decades, there have been a number of new medications which can be used, but unfortunately, many patients continue to have seizures despite these. Overall, only 2/3–3/4 of patients can be seizure-free on medication [2]. Studies have shown that patients with intractable seizures undergoing surgery are significantly more likely to be seizure-free after surgery than if they continue on medication alone [3]
Temporal lobe seizures
Temporal lobe seizures are the most commonly evaluated for surgery. Onsets of seizures from the temporal lobe can include epigastric, olfac- tory, and gustatory sensations, emotional chan- ges, sense of familiarity or strangeness, hallucinations, staring, and automatisms, among others. One review [4] concluded that with temporal lobe epilepsy, abdominal aura had a 52% sensitivity and 90% specificity for localiz- ing seizures to the temporal lobe. Seizures arising from temporal neocortex can have similar symptoms. For example, basal but not mesial temporal seizures can present with behavioral arrest or motor changes. Ictal theta activity was found to have an 85% probability for temporal lobe epilepsy and was 80–94% correct with respect to the side of seizure onset. Lateralized interictal spikes and possibly contralateral hand dystonia also were helpful. The authors thought that some of these also might help differentiate mesial from lateral temporal lobe epilepsy. Febrile seizures are thought to have a rela- tionship with mesial temporal sclerosis, as is found with mesial temporal lobe epilepsy; one report [5] found that only 2/21 patients with neocortical temporal lobe epilepsy had a history of febrile seizures. Seizure-free intervals were found to be less common with neocortical tem- poral lobe epilepsy than with mesial onset tem- poral lobe epilepsy. Despite neocortical onset, there nonetheless could be mild hippocampal atrophy. Patients could have tumors or hetero- topias. About half could have decreased memory function on the Wada test. Independent con- tralateral spikes were rare. Some patients had experiential auras or motionless stares.
Frontal lobe seizures
Frontal lobe epilepsy symptoms vary with the site of seizure onset [4]. With superior or inter- hemispheric onsets, there can be contralateral
eye, head, or body turning with tonic or dystonic posturing. Orbital frontal seizures can include unusual behaviors including hypermotor activity such as rapid leg kicking or bicycling and can have autonomic findings, behavior arrest, and automatisms of other types. These characteristi- cally occur frequently during sleep and last a relatively short period of time. Seizures from the frontal operculum can include salivation and swallowing. Inferior frontal onset can include findings referable to the face or to speech. Dor- solateral or dorsomedial onset seizures can include contralateral motor findings, premotor area seizures tonic version, and supplementary motor area seizures speech arrest, fencing pos- tures, bilateral motor findings, and head version. It is important to note that frontal lobe regions can produce seizures that are similar to one another.
Insular seizures
Seizures from the insula can include visceral, gustatory, and somatosensory symptoms, including laryngeal constriction or paresthesias [4].
Parietal and occipital seizures
Parietal lobe seizures can begin with somatosensory phenomena, and occipital lobe seizures can begin with visual auras and phe- nomena. However, both parietal and occipital lobe seizures can be locally silent, with symp- toms related to the area of projection. For example, parietal lobe seizures can imitate superior frontal lobe seizures or can have sen- sorimotor symptoms.
Noninvasive Evaluations
Neuropsychological evaluation is important both in assessing baseline functioning and in deter- mining whether there are aspects of function, which are below expectations. At times, these functions can be localized to specific regions of the brain, which in turn might be the sites of origin of the patient’s seizures.
The intracarotid sodium amobarbital or Wada test is performed less frequently now than had been the case in the past. When used, it has two purposes. With the test, a medication, which “anesthetize” one hemisphere for a few minutes while the other is tested. One looks for language function during the period of “anesthesia,” to see whether speech remains while the hemisphere is not functioning, and one presents items for the patient to remember. One also tests recall mem- ory after the effects of the medication wear off, to see whether new memories could be encoded during the period of hemisphere inactivation. The idea is that if a function is intact during the period of drug-induced inactivation, the tested function is likely to be supported by the non-inactivated hemisphere.
Imaging is increasingly important in evaluat- ing patients with intractable seizures, with mag- netic resonance imaging (MRI) being the most important; one should always be performed if possible. Important findings include evidence of mesial temporal sclerosis or other abnormality, as well as evidence of tumor, dysplasia, vascular anomaly, developmental defects, or other chan- ges. For patients with temporal lobe epilepsy, it is important to keep in mind that there can be bilateral atrophy on MRI in some patients, per- haps 20% [4]. Sometimes, surgery can nonethe- less be performed on one side, if seizures only originate on that side, but it adds a consideration before deciding whether to operate and a con- sideration when counseling the patient with respect to possible postoperative memory prob- lems. Neuroimaging [4] can show amygdala abnormalities in 55% of patients and changes in the enterorhinal cortex in 25% and in the fornix in 86%. In one study of patients with temporal lobe epilepsy and tumors [6], astrocytomas were found in 46%, gangliogliomas in 21%, oligo- dendrogliomas in 18%, dysembryoplastic neu- roepithelial tumors in 6%, anaplastic astrocytomas in 6%, and meningiomas in 3%.
Dual pathology can occur in 15–52% of patients with hippocampal sclerosis, with eti- ologies including heterotopias, cortical dysplasia, and tumors. Vascular lesions including cav- ernous malformations and arteriovenous malfor- mations can occur in about 5% of patients [4]. Although the term has often been used to describe the combination of hippocampal scle- rosis plus another lesion, it also is used to describe the occurrence of two potentially epileptogenic lesions regardless of type.
Causes of extra temporal seizures in a series of 133 consecutive cases included [7] cortical dysplasia in 38% and tumor in 28%. They reported that 10/50 patients with cortical dys- plasia also had tumors; 11/50 had infarcts or remote ischemic lesions. They found four with arteriovenous malformations, 3 with Sturge– Weber malformations, and 2 with Rasmussen’s encephalitis. 17% had no significant findings.
Positron-emission tomography (PET) scans can point to areas of decreased metabolic func- tion which in turn can be area of epileptogenesis. Single-photon emission computed tomography (SPECT) studies can point to areas of altered function in a similar way with similar inferences regarding whether these might indicate where seizures are originating. Magnetic resonance spectroscopy (MRS) can point to areas with altered chemistry. fMRI is being developed as a possible alternative to the Wada test, using it to localize language, which has been relatively successful, as well as memory, which has not been as successful thus far.
Often noninvasive evaluation is sufficient to determine how and where to operate, but some patients need implanted electrodes as well. Depth and subdural electrodes are the ones principally used. Depth electrodes are thin “tubes,” each usually containing several elec- trodes and electrode wires, and which are directed through the skull and through the outer cerebral tissues, aiming at more medial locations such as mesial temporal lobes. However, there are electrodes along the tube so that more lateral locations including neocortex are recorded at the same time. Subdural electrodes are flat disks, usually a few millimeters in diameter, imbedded in Silastic or other plastics and placed over and around areas of interest. Both depth and subdural electrodes are used to localize the area of seizure onset. Subdural electrodes are commonly, and depth electrodes less commonly, stimulated electrically to determine the relationship of the area of seizure onset to regions controlling important functions such as movement, sensa- tion, and language.
Complications of depth electrodes include asymptomatic subdural bleeding gliosis, degen- eration, and microabscesses along electrode tract [8–10]. The incidence of bleeding or infection is between 0.5 and 5%. There can be a 25% overall rate of complications with subdural electrodes [11], including 12% infection, 11% transient neurological deficits, 2.5% epidural hematoma, 2.5% increased intracranial pressure, 1.5% infarction, and 0.5% death. Cerebrospinal fluid leakage also was common. The authors found that complications were more likely if there were more than 60 electrodes and if the grid was left in more than 10 days. Other risks included older patients, left-sided placement, and additional burr holes. They observed that complication risk likely was less now with improved technique.
Functional localization in epilepsy surgery
Functional localization can be performed in one of two ways. One can alter the brain, for example with cortical stimulation, and assess the behav- iors that occurred during the alteration. An example would be to see whether there is hand or other movement during stimulation. One also can alter behavior and then assess the brain during the behavior. An example might be asking the patient to begin to read and then seeing whether there is reading arrest during stimulation. Corti- cal stimulation is generally performed with recurrent pulses. These should be alternating in polarity, so that the resulting stimulation is charge-balanced, to avoid complications due to metal deposit on an electrode. We [12] have used 0.3-ms duration alternating polarity square wave pulses, delivered at 50 pulses per second, with stimulation duration varying but generally 1–2 s initially and then up to about 5 s for language testing. Intensities that are needed to obtain stimulation-induced changes vary; with the device we use, they can go up to 17.5 mA. It important to emphasize that the reliability of results can depend on the intensity of stimulation. If you stimulate at too low an intensity, you can get a false-negative result. If you stimulate at too high an intensity, you can get afterdischarges which can produce false positives because of the spread of the afterdischarges and also can cause seizures. One should begin at a low intensity, 0.5–1 mA, and increase in increments of 0.5– 1 mA. Keep in mind that the above is in mil- liamps, but the important parameter is charge density, which depends on not only current but also electrode surface area.
It is also important to emphasize that stimu- lation only assesses the cortex directly under the stimulated electrodes. Charge density drops rel- atively rapidly with increased distance from the actual location of the electrodes. Also, 7/8 of the current is shunting through the cerebrospinal fluid [13, 14].
In addition to stimulation, one can analyze the brain function with a variety of methods based on frequency or power analysis. In summary, one asks the patient to perform an activity which can be something simple such as moving the tongue, making a fist, or wiggling the toes. One then records brain activity before during and after this activity and sees whether there are changes in particular regions of the brain which might point to the area participating in controlling this activity. There [15, 16] is a relatively good cor- relation between the results of such analyses and the results of cortical stimulation, but the two methods are slightly different so that the regions localized with one technique or the other might be expected to, and in fact do, differ.
There are controversies regarding what to remove. For example, for anterior temporal lobectomy, some perform the same standard resection on each patient, while others tailor the resection based upon the specific findings during evaluation, particularly evaluation with implanted electrodes. Some surgeons perform an amygdalohippocampectomy with lateral tempo- ral structures left relatively intact. Some will do a hippocampectomy alone. There has been interest in the use of radiosurgery and laser surgery as noninvasive ways of resecting only mesial tem- poral structures.
In a prospective study [17], Wiebe et al. com- pared 40 patients who underwent temporal lobectomy to 40 who were on a surgical waiting list for a year. The surgery was an en bloc resec- tion of 4–4.5 cm of the dominant and 6–6.5 cm of the non-dominant, temporal lobe, with removal of amygdala and 1–3 cm hippocampus. One year later, 58% of patients with surgical treatment but only 8% of patients with medical treatment alone were free of episodes with loss of consciousness. Quality of life also improved in patients who had surgery. However, simple partial seizure may continue: This group previously found [18] that 93% of surgical and 13% of medical patients had a 90–100% reduction of seizures after 6 months but only 35% of the surgical patients (and 6% of the medicine alone patients) were completely seizure-free. Also, seizures can recur over time. In one review [19] of patients seizure-free at one year, 87–90% were seizure-free at 2 years, 74– 82% at 5 years, and 67–71% at 10 years. Among patients who were seizure-free at 2 years, 95% were seizure-free of 5 years, 82% at 10 years, and 68% at 15 years. Therefore, with time, seizure control decreases, but the longer the patient was seizure-free, the better the outcome. This review noted that more than half of the patients would have their seizure recurrence in the first 6 months and 95% in the first 5 years. They found that incomplete resection was more likely in patient with seizure recurrence. They also noted the possibility of a “running-down” phenomenon with initial seizure recurrence followed by seizure control. Good prognostic factors included early onset of seizures, mesial temporal sclerosis with ipsilateral interictal EEG discharges, unilateral MRI, PET, and SPECT findings with a single lesion, and greater than 90% of the interictal EEG findings originating in one place. Poor prognostic factors included a long duration of seizures and the occurrence of generalized tonic–clonic seizures. If patient has a normal MRI, outcome can be good if there are ipsilateral interictal EEG discharges and a history of febrile seizures. Out- come can be worse in patients with tumors, cor- tical dysplasia, vascular disease, and a longer duration of epilepsy [4].
One review [4] concluded that after surgery for temporal lobe tumors, 65% of patients became seizure-free and 82–86% of patients were free of disabling seizures. For mesial tem- poral sclerosis, 75% of patients became seizure-free with 41–79% free of disabling sei- zures. Among patients with normal MRIs, 56– 62% of patients became seizure-free. For patients with cortical dysplasia, 38–54% became seizure- free. For patients with dual pathology, in this case mesial temporal sclerosis plus another lesion, 73% became free of disabling seizures if both pathological areas were removed but only 20% if only one of the areas was removed.
Schmidt et al. [20] reviewed previous reports of a total of 1658 patients who had been off medication for 5 years. They found that 25% of adults and 31% of children became seizure-free and remained off medication for 5 years.
Surgery outcome has long been classified using a system devised by Engel [21]. In this, Class I is for patients “free of disabling seizures,” but the subcategories include completely seizure- free since surgery, non-disabling simple partial seizures only, some disabling seizures but none for 2 years, and generalized convulsive seizures with medication discontinuation. Class II was for patients with rare disabling seizures, with sub- categories of initially free of disabling seizures, rare seizures now, rare disabling seizures since surgery, more than rare disabling seizures but rare for the last two years, and nocturnal seizures only. Class III was defined as worthwhile improvement, with subcategories of worthwhile seizure reduction and prolonged seizure-free intervals of greater than half the follow-up per- iod and at least two years. Class IV was for patients with no worthwhile improvement, with subcategories of significant seizure reduction, no change, or worsening of seizures. The classifi- cation system was revised by a committee of the International League Against Epilepsy [22]. In this classification, Class 1 was for patients completely seizure-free with no auras beginning one month after surgery, Class 2 for patients with auras only, and class 3 for patients with 1–3 seizure days per year. Class 4 was for patients with seizures ranging from 4/year to 50% decrease in days with seizures. Class 5 was for patients with a 50% reduction to 100% increase in days with seizures. Class 6 was for patients with a greater than 100% increase. Classes 3–6 included patients with or without auras
Other outcomes in temporal lobe surgery
Memory often can be worse [23]: (a) after a dominant hemisphere temporal lobe resection, (b) if the MRI does not show exclusive unilateral mesial temporal sclerosis, and (c) if preoperative immediate and delayed recall memory is intact. In particular, there can be declines in object naming and similar functions. Memory can improve, however, if a nondominant resection is performed. Surgery can be successful [19] if depth recordings show a unilateral ictal onset, if there is ictal spiking but not a rhythmic fast pattern, if there is no evolution to a distinct contralateral seizure pattern, and if there is an interhemispheric propagation time greater than 8 s. As expected from the last of these, a longer duration of ictal EEG activity before clinical onset may at times point to a more successful surgical result. Also, results of temporal lobe surgery are better if the onset of the seizure is not diffuse on the recordings and does not begin in the posterior temporal regions where resection is more difficult [19]. With bilateral ictal onset, surgery can still be successful if greater than 50% of seizures originate from the resected side, and if the Wada test shows adequate memory on the other side with no extra temporal focus [24]. In this study, 9/11 operated patients had no seizures and one of 11 had a 75% reduction in seizure frequency. Explanations for the findings included the possibility of a mirror focus, disconnection, or bilateral disease which was nonetheless responsive to unilateral surgerAdverse effects [4] after temporal lobe epi- lepsy surgery can occur in about 2% of patients including quadrantanopsia and memory prob- lems. There can be other field deficits as well as motor, sensory, or speech deficits. With anterior choroidal artery or other occlusions, there can be significant problems including strokes. Some patients have had cerebellar hemorrhages. Death has been reported to occur in 0.24% of patients. One review [25] found less than 1% morbidity including hemorrhage, infarction, pulmonary embolus, and pseudogout. There was a 2.4% incidence of hemiparesis and 50% incidence of visual field defects with 2–4% hemianopia. Less than 2% of patients had infection and epidural hematoma or transient third nerve palsy, 20% transient anomia, 1–3% persistent dysphagia, and 2–20% transient psychosis or depression.
Depression is commonly present prior to temporal lobectomy and is more common after- ward if present prior to surgery. Patients with a history of depression are less likely to become seizure-free after surgery. Moreover, there is a risk of postsurgery suicide, with an age- and sex-adjusted mortality ratio of 13.3 compared to the US population as a whole [26]. On the other hand, a study found that 45% of a group of patients experienced remission of psychiatric symptoms, no longer needing psychotropic medication, after epilepsy surgery [27].
Frontal lobe surgery outcomes
In one survey [19] of frontal lobe surgery patients, at one year 49.5% of patients had Class I onsets with 55.7% of these patients seizure-free. In 5 years, 47% had Class I seizure control and 30.1% of these were seizure-free. At 10 years, 41.9% had Class I outcome. 80% of recurrences were in the first 6 months. If there were recur- rences, patients were less likely to become seizure-free. The running-down phenomenon was less frequent. Good prognostic factors included MRI lesions and complete resection. With these, the likelihood of good prognosis was 72% versus 41% if these were not present.
Outcomes with parietal or occipital epilepsy surgeries
The same authors concluded that with parietal and occipital lobe seizures, 73.1% of patients were seizure-free in 6 months, 68.5% in one year, and 54.8% in 6 years. Circumscribed lesions conveyed a good prognosis. The authors noted that side effects such as dysphagia or Gerstmann’s syndrome could occur and they discuss the importance of sparing the calcarine cortex and speech areas.
MST
When a region of seizure onset cannot be removed completely, multiple subpial transec- tions can be considered [29, 30]. This involves separating the superficial cortical horizontal connections within a gyrus while preserving the vertical pathways. Often, this is performed adjacent to an area of resection. Transections are typically performed at approximately 5-mm intervals, with the cuts extending 1–3 mm. The concept is that this disrupts “horizontal” epilep- togenic propagation while preserving “vertical” axonal connections. One should keep in mind that this affects the gyral crown but not the sulci because of the way this is done. Reports describe that 1/3–2/3 of patients become seizure-free, but later recurrences also are possible. Although the major gyral sulci are well known, it is important to realize that there are microsulci throughout the cortex which are not readily seen from the cor- tical surface and that fibers in the microsulci are not affected by this technique. Also, microscopy shows that transections produce not only fiber separations but also microlesions [31].
Hemispherectomy
Hemispherectomy is a useful for seizure control in a small group of patient who have problems such as Rasmussen’s syndrome, hemimegalencephaly, Sturge–Weber syndrome, or lesions such as porencephaly with seizures that have become intractable to medication [32]. Often, these patients have multiple seizures per day and have a complete or progressive hemi- paresis. There are widespread areas of potential epileptogenesis in a single hemisphere. The entire hemisphere is removed in the classic procedure, but there are modifications including a functional hemispherectomy, in which the hemisphere is left in place but disconnected from the opposite hemisphere by section of pathways such as the corpus callosum. To avoid postoperative compli- cations, some surgeons will collapse the subdural space by fixing the dura to the falx. Corticectomy plus disconnection has been performed as well as corticectomy plus lobectomy. 70–80% of patients become seizure-free. Because of the reduction in seizures, intellectual function often improves. Despite removal of a hemisphere, patients can walk or even run although they may need an ankle brace. The hand contralateral to the resected hemisphere has no fine finger and has little wrist movement but can function as a “helper hand.” Possible complications include subarachnoid bleeding, hemosiderosis, cerebrospinal fluid block, and hydrocephalus.
Multilobe resections
Multilobe resections can be performed as well. For example, this can be done in patients with Sturge–Weber syndrome, or with cortical dysplasia, with the dysplasia removed as an addendum to temporal lobe resection. These methods have not been helpful in patients with Rasmussen’s syndrome; hemispherectomy is the surgical treatment of choice. As expected, func- tional complications of hemispherectomy or multilobar resection often relate to the location of the area of surgical removal. In particular, removal of the perirolandic area is more likely to result in a permanent motor deficit. (But patients with Rasmussen’s syndrome often are already hemiparetic when surgery is performed.)
